Polyamines (PA) are organic cations found in all organisms, and their synthesis occurs in the cytoplasm of all cells. Polyamine research dates back several centuries; in 1678 Van Leewenheuk saw crystals in semen that were later identified as spermine.
The following text points out several possibilities and chemical pathways in which “Intume” chlorine dioxide intervention can destroy tumors and prevent proliferation of cancer cells. Removing all polyamines is a main objective, but at the same time neutralizing other systems that aid the neoplasm also appears to be important. Chlorine dioxide (ClO2), a strong oxidant, can safely be injected into a subject's body, including a tumor, although the compound has not yet been utilized as a cancer treatment in this manner. ClO2 is highly penetrating, and generally considered non toxic—as demonstrated by its application in deep wounds, 3rd degree burns, and use in oral and topical diseases.i,ii,iii,iv,v,vi,vii,viii 
Cancer cells are rich in polyamines which is necessary for survival and growth of tumors.ix Capacity of cancer tissue to produce abundant PA likely contributes to cancer cell's higher growth rates.ixx High concentrations of PA enhance cancer cells to invade, and is associated with less apoptosis and increased expression of the genes affecting metastasis.ix.xi The association of increased polyamine synthesis and cancer was first reported in the late 1960s. Interest in targeting polyamine metabolism as a potential strategy for cancer chemotherapy was stimulated in the early 1970s.xi From the late 1970s and throughout the 1980s the endogenous polyamine inhibiting compound, difuoromethylornithine (DFMO), was actively evaluated as an anticancer drug. Unfortunately, the attempt at inhibition of PA synthesis, as well other chemical intervention, has proven to be generally ineffective as an anticancer strategy in clinical trials.xi Surprisingly, similar experiments were successful in in vitro and on animal models. Inhibition of polyamine by DFMO in animal experiments reduced tumor growth and decreased the amount of metastasis, resulting in prolonged survival of the animals.ix With the introduction of the present “Intume Oxidant,” polyamine synthesis will be halted by ClO2 oxidation of existing PA, along with oxidation of PA precursor molecules, arginine and ornithine. In addition, the thiol, ODC, which mediates PA manufacture within cancer cells by reducing DFMO, will also be oxidized by ClO2.
PA concentrations in blood and urine of cancer patients reflect the levels of PA synthesis in cancer tissues.xi Concentrations in the blood may vary widely in healthy individuals; however, cancer patients with increased PA levels in blood or urine are reported to have more advanced disease and worse prognosis.xi,xii Increases can also predict relapse of the disease.xi 
Chlorine dioxide will oxidize polyamines, and the resultant oxidation products, hydrogen peroxide and aldehydes, are both highly toxic to the cancer cell itself.xiiixivxv Normal cells contain much smaller amounts of PA and will not be affected as much. The increased hydrogen peroxide produced by the oxidation can cause cancer cells to undergo apoptosis, pyknosis, and necrosisxvi—some of the physical controls the body uses to remove cancer cells. The chemical result of chlorine dioxide oxidation may be similar to the endogenous hydrogen peroxide's removal of the cancer cell. Normal cells are considerably less vulnerable to peroxide, or any oxidation, due to the greater amount of catalase reducing agent in the non-transformed cell.xvii 
Direct injection of Intume ClO2, a relatively non toxic oxidant, would better substitute the body's natural intracellular hydrogen peroxide. For general topical use on disease, peroxide cannot be applied to bad wounds, due to its cytotoxicity.xviii Chlorine dioxide on the other hand, when used to treat disease, is an aid to healing and prevents scarring.xix,ii It is often used by veterinarians on bad infections,vi and applied experimentally on people for non healing wounds like diabetic ulcers. Twenty five years of difficult internal applications has indicated no adverse events,vi except that of oxidizing red blood cells. No other antiseptic—for example, chlorhexidine, hydrogen peroxide, hypochlorite, or silver ions, are acceptable for disinfection of deep wounds.
Amine oxidase, an extracellular oxidant and biological regulator, also oxidizes polyamines yielding cytotoxic products. Cancer cells with their high PA content would be inactivated preferentially by a strong oxidizing agent. When amine oxidase was microinjected into cultured fibroblasts of chick or rat embryos, a slight temporary inhibition in DNA and protein synthesis was observed.14 But after these normal fibroblasts were transformed by virus, they were more susceptible to the injected enzyme than the normal cultures. Similarly, when the oxidase was injected into tumor bearing animals, there was a “remarkable decrease” in tumor growth.xiv 
Another endogenous oxidizing agent, nitric oxide, is also involved in destroying tumor cells. In this case the NO oxidant is released by macrophages.xx 
ClO2 will oxidize thioles, phenols, purines, secondary and tertiary amines; also tyrosine, tryptophan, and histidine.xi Most heavy metals are oxidized also. All of these compounds are involved with tumor metabolism. Inhibiting these and key enzymes will disrupt tumor proliferation.xiii Almost all sulfur bearing molecules can be oxidized by ClO2 if the sulfur is not in the form of sulfate
Elevated rates of reactive oxygen species (or ROS) have been detected in almost all cancers.xxi,xxii They promote many aspects of tumor development, DNA damage, growth, proliferation and angiogenisis.xxi,xxii These highly reactive oxidants will be neutralized in an oxidation/reduction reaction with ClO2, similar to the better known in vitro chemical effect of chlorine dioxide with common oxidants, hypochlorite, ozone, or peroxide. Direct contact of ClO2 in the cell would overcome the cancer increasing ROS effect.
Cancer cells in the process of synthesizing polyamines is also associated with increased production of proteinases such as serine proteinase, metalloproteinases, cathepsins, and plasma activator, all of which tend to degrade surrounding tissue, permitting cancer cell passage.ix Many investigators have been concerned with enzyme activity disrupting this important extra cell matrix (ECM),xxiii and also the activity in the surrounding stroma connective tissue. Some proteases also catalyze activation of growth factors and thus regulate growth of primary tumors as well as permit metastases.xxiv ClO2 should easily neutralize sulfur bearing proteases involved.
Tumor cells produce collagenase proteolytic enzyme which occurs at a higher level than in corresponding benign tissues.xxv The ability of transformed cells to invade surrounding tissues strongly depends on collagenase (MMP) since this particularly active proteinase degrades the structural components of the ECM and cell-cell adhesion molecules. The first evidence that collagenase played a role in preventing cell invasion is derived from in vitro experiments in which addition of collagenase inhibitors blocked tumor escape into the ECM.xxv Collagenase, like other sulfur bearing enzymes is easily oxidized.xxvi The enzyme is also inactivated at the low pH of Intume.
Cancer cells can take up PA from their surroundings, and also export PA to the extracellular space as well.xi Because of this, adding Intume solution surrounding the tumor may be a reasonable anti neoplastic action. Increased PA uptake by immune cells results in reduced cytokine production of tumor necrosis factor, otherwise needed for antitumor activities.ix Adhesion molecules are also affected by this secreted PA.ix
For cancer cells to invade, favorable chemical interactions must take place between cancer cell and the stroma framework,xxvii,xxvii,xxix Several papers describe this signal pathway as “crosstalk,”xxvii and interplay between the two adds to the progression of tumors and metastasis. Intume chemical action would likely interrupt this neoplastic link by targeting both tumor and surrounding stroma.
The cytokine, Interleukin 6 (IL-6), a mediator of inflammation, steadily increases in the blood as cancers become more life threatening.xxx Il-6 is regarded as an important tumor promoting factor in many types of human cancers.xxx The compound contains disulfide bonds, which will be oxidized by ClO2.
Glutathione reducing agent serves important functions within cells, but its rapid synthesis in tumor cells is also associated with high rates of cellular proliferation and cancer growth.xxxi Removing glutathione by oxidation would then inhibit this tendency of cancer spread, as well as, indirectly enhance the effectiveness of subsequent standard therapy. Radiation and chemotherapy depend on the cidal oxidation by hydrogen peroxide which is removed by glutathionexxxi,xxxii 
Depletion of glutathione appears therapeutically effective only when low levels can be achieved,xxxii and several drugs have been tried in the past for reducing glutathione, but found to cause damage in normal tissue.xxxi,xxxii However, excess ClO2 in and around the cancer cell or nodule would not be expected to have a particularly adverse effect on surrounding normal tissue or organs as do other anticancer compounds, except for its oxidation of hemoglobin. Previous experience has shown that ClO2 does not irritate neighboring tissue when used as an antiseptic on bad wounds and diseases. In tissue culture experiments, highly diluted chlorine dioxide is able to kill bacteria within a normal cell without injury to the cell itself.xxxiii,xxxiv,xxxv,xxxvi 
Chlorine dioxide is a good penetrant, soluble in water, oil, serum, saliva, and in a wide range of pH. As an example, when applying ClO2 as an antiseptic topically, the oxidant treats fungus of the nail, a difficult disease to cure, by penetrating the nail and tissue around the nail. When applied to warts, the thickened tissue is penetrated, killing the papilloma virus within. Ring worm on cats is successfully treated by apparently entering the hair follicles and killing the fungal spores; surprisingly, no other topical medication works well for ring worm on cats. When placed on rats in a 60% of the body 3rd degree burn, no toxicity was indicated.i If ClO2 is placed on a wound for disinfection, the metabolized oxidant products, chlorite and chloride, are absorbed in the body and are eliminated rapidly in the urine.xxxvii,xxxvii,xxxix,xl Many ingestion studies by the EPA in animals and humans have been performed with ClO2 displaying few, if any, adverse effects.xxxviii 
Chlorine dioxide is not the first anticancer compound to be injected into tumors, but probably the only percutaneous such compound relatively safe on non transformed tissue, and suitable for contacting internal organs. For about 25 years, 50% acetic acid, and 100% ethyl alcohol, has been injected into animal and human liver tumors.xli Both these compounds are normally considered corrosive and irritating, but nevertheless they are effective in ablating liver cancer cells with low morbidity—at least in the short run. It is surprising that highly toxic treatments would be utilized on liver cancers since a majority of these patients have underlying liver disease and are at high risk for recurrent disease and of progression to liver failure.xlii In one fairly large study evaluating 102 liver cancer patients where acetic acid was used to necrotize cancer cells, it states, “Even in well selected patients, the high rate of recurrence of multifocal hepatocellular carcinoma underline the limits of this method as well as all other percutaneous strategies.”xliii In any case, because of Intume's relatively low toxicity, liver tumors larger than 3 cm might be treated with curative intent, or just as a palliative therapy not possible now. Further, Intume intervention is not specific to one type of tumor as is the case with acetic acid and ethyl alcohol on liver tumors. ClO2 treatment could also be described as the removal of vital constituents, and not just gross obliteration of tissue that occurs with heat, radiation, or strong chemicals such as acetic acid.
The history of putting oxygen releasing substances into the body follows several tracks.xliv,xlv Interest in ozone dates back to the mid 1800s in Germany, where it was claimed to purify the blood. One of the earliest accounts of the medical use of hydrogen peroxide was a short article in 1888 in the Journal of The American Medical Association.xliv A physician described a case where peroxide was useful in removing pus from the nose and throat of a child with diphtheria; and also recommended using peroxide for cancer of the womb—as cleanser, deodorizer, and stimulator of healing.xliv During World War 1, doctors used ozone to treat wounds, trench foot, and the effects of poisonous gas. In the 1920s, ozone and peroxide injections were used experimentally to treat the flu. In 1920 peroxide injections were used on patients during an epidemic of viral pneumonia.
Alternative Medicine practitioners claim that cancer cells thrive in low oxygen environments, and adding oxygen to the body creates an oxygen rich condition in which cancer cells cannot survive. Use of ozone or oxygen in small amounts under controlled conditions for treating limited parts of the body has shown some success in mainstream medical research.xliv,xlv Another “alternative” theory approach involved hydrogen peroxide and also chlorine dioxide taken by mouth or injected into a vein—all well short of FDA aegis. For good or ill, practitioners promote oxygenation for use rectally, vaginally, as a nasal spray, as a soak, and as ear drops.
With the Intume ClO2 therapy proposed now, many types and sizes of tumors have a good chance to be destroyed; a welcome option when other methods of removal cannot be tolerated. Injection by Intume would be particularly valuable, for example, when a small part of the tumor is in intimate association with nerves, vessels or cartilage, and complete removal of the tumor not possible by surgery; or a gratifying substitution to avoid unpleasant side effects of present therapies. Just slowing the growth of a large recalcitrant tumor can extend someone's life, or quality of life. Ethanol injection therapy and radio frequency ablation have been used on liver tumors as a large as 10 to 12 centimeters in diameter as palliative therapy, in order to increase patient survival rate.xlvi 
A direct approach into the tumor with Intume would probably not cause adverse events elsewhere in the body as did DFMO in human trials. In a Review Article comparing therapies for liver tumors, “Although surgical resection is generally preferred for curative ablation, the long term survival rates following resection are no better that those following local ablation.”xlvii For many years research on cancer has largely been ruled by the view that genetic mutations drive tumor growth. However, cancer may be as much a disease of disturbed microenvironment as it is a result of disturbed genes.xlviii The tumor microenvironment composed of non-cancer cells and their stroma has become recognized as a major factor influencing the growth of cancer.xxvii Alterations of cell shape and of the cell's surroundings may actually precede the onset of tumors and even initiate the disease.xlviii The area around a particular surgical site could be saturated by oxidative Solution with the prospect of preventing neoplasm transformation.
Tumors may be injected by ultrasound guided needles similar to guided biopsy probes, or by CD fluoroscopy. Conceivably metastasized tumors might be treated with a needle injection; and in the case of a very large tumor, many injections can be made in a single therapy session. The hypoxic core of the tumor may be an ideal place to inject chlorine dioxide. The strong oxidant would no doubt disrupt or neutralize the hypoxic area already weakened by lack of blood flow. Hypoxia, a common condition in cancer tissues, exerts a strong pressure on cells to separate from the tumor cluster and migrate into circulation.ix
By injecting Intume oxidant, and thereby removing the natural reducing molecules, catalase and glutathione within and around the cancer cell, tumors could then be more easily treated, as stated previously, by relatively low doses of oxidizing therapies such as radiation and chemotherapy.xi xlix 
Both DFMO and NSAIDS taken orally by animals have been shown (in animals only) to reduce cancer. These compounds treat neoplastic disease each by different chemical route.xi They also worked additively in inhibiting cancer of the colon and intestine in murine models.xi Since Frontier's Intume would probably remain active for only a few hours after each injection, adding these two options, to the patient as well as others, on an oral ongoing basis, could conceivably remove weakened or nascent tumor cells remaining. Although the Intume oxidative interaction may by relatively short, the kind and variety of new molecules produced in the debris field could likely recruit an immune response for some time.1 Conceivably there may be a salutary effect on distant metastasis, as well. Athymic mice, however, now proposed for the first tumor studies, would not have any additive protective immune ability.
An immunosuppressive rebound that sometimes takes place in human anti cancer therapy may not as easily occur in the case of Intume treatment since too much of the transformed cell and associated environment will be disrupted. There is a reasonable chance also that the great number of new cellular particles and molecules, along with an influx of T cells and neutrophils, would choke off blood vessels and the tumor's nutrient supply.1 
In 1978, the present inventor was the first to patent the idea of placing ClO2 on the body to cure disease. Since then, more than 200 patents have been issued for animal topical application. Applications varied from scratches to deep wounds, from fungus infections to viral, and bacterial, and yeast, from fungus of the nail to sun keratoses on the scalp. Ear infections, and sinus infections. From mouthwash cleaning to bad acne infections. Colds and sore throats and wart removal and deep wounds.
Much to the chagrin to the FDA, people also drank ClO2 for internal applications like intestinal and stomach diseases and also malaria, and even autism. These applications are quite doubtful and even dangerous and are packaged and sold from Mexico. ClO2 was used to purify the blood even though ClO2 can not exist in blood and was never found in the blood. It is too strong an oxidizing agent. Blood is filled with reducing agents that would immediately neutralize ClO2: glutathione, catalase, super oxide dismutase, vitamins, minerals, to name a few. One of the well known drawbacks to the topical application of ClO2 is the need to measure two parts first, mix them, and usually wait a few minutes, before applying. Also in the usual course of ClO2 application the pH needs to be quite acidic, normally below 3 in order to release the needed amount ClO2 from the salt sodium chlorite. Many times the pH was too low for wound or disease application. Finally ClO2 can not be easily stored as it is a gas and must be released just before use. Since ClO2 release from chlorite is continuous so that the concentration is a moving target when applying to a disease.